IMpower210:A phase Ⅲ study of second-line atezolizumab vs. docetaxel in East Asian patients with non-small cell lung cancer

Objective: IMpower210(NCT02813785) explored the efficacy and safety of single-agent atezolizumab vs.docetaxel as second-line treatment for advanced non-small cell lung cancer(NSCLC) in East Asian patients.Methods: Key eligibility criteria for this phase Ⅲ, open-label, randomized study included age ≥18 years;histologically documented advanced NSCLC per the Union for International Cancer Control/American Joint Committee on Cancer staging system(7th edition);Eastern Cooperative Oncology Group performance status of 0 or 1;and disease progression following platinum-based chemotherapy for advanced or metastatic NSCLC. Patients were randomized 2:1 to receive either atezolizumab(1,200 mg) or docetaxel(75 mg/m^(2)). The primary study endpoint was overall survival(OS) in the intention-to-treat(ITT) population with wild-type epidermal growth factor receptor expression(ITT EGFR-WT) and in the overall ITT population.Results: Median OS in the ITT EGFR-WT population(n=467) was 12.3 [95% confidence interval(95% CI),10.3-13.8] months in the atezolizumab arm(n=312) and 9.9(95% CI, 7.8-13.9) months in the docetaxel arm[n=155;stratified hazard ratio(HR), 0.82;95% CI, 0.66-1.03]. Median OS in the overall ITT population was 12.5(95% CI, 10.8-13.8) months with atezolizumab treatment and 11.1(95% CI, 8.4-14.2) months(n=377) with docetaxel treatment(n=188;stratified HR, 0.87;95% CI, 0.71-1.08). Grade 3/4 treatment-related adverse events(TRAEs) occurred in 18.4% of patients in the atezolizumab arm and 50.0% of patients in the docetaxel arm.Conclusions: IMpower210 did not meet its primary efficacy endpoint of OS in the ITT EGFR-WT or overall ITT populations. Atezolizumab was comparatively more tolerable than docetaxel, with a lower incidence of grade3/4 TRAEs.

Molecular heterogeneity of anti-PD-1/PD-L1 immunotherapy efficacy is correlated with tumor immune microenvironment in East Asian patients with non-small cell lung cancer

Objective:The aim of this study was to investigate how the tumor immune microenvironment differs regarding tumor genomics,as well as its impact on prognoses and responses to immunotherapy in East Asian patients with non-small cell lung cancer(NSCLC).Methods:We performed an integrated analysis using publicly available data to identify associations between anti-programmed death 1(PD-1)/programmed death-ligand 1(PD-L1)immunotherapy efficacy and classic driver oncogene mutations in East Asian NSCLC patients.Four pooled and clinical cohort analyses were used to correlate driver oncogene mutation status and tumor microenvironment based on PD-L1 and CD8+tumor-infiltrating lymphocytes(TILs).Immune infiltrating patterns were also established for genomic NSCLC subgroups using the CIBERSORT algorithm.Results:Based on East Asian NSCLC patients,TIDE analyses revealed that for anti-PD-1/PD-L1 immunotherapy,epidermal growth factor receptor(EGFR)-mutant and anaplastic lymphoma kinase(ALK)-rearranged tumors yielded inferior responses;however,although Kirsten rat sarcoma viral oncogene homolog(KRAS)-mutant tumors responded better,the difference was not statistically significant(EGFR:P=0.037;ALK:P<0.001;KRAS:P=0.701).Pooled and clinical cohort analyses demonstrated tumor immune microenvironment heterogeneities correlated with oncogenic patterns.The results showed remarkably higher PD-L1-and TIL-positive KRAS-mutant tumors,suggesting KRAS mutations may drive an inflammatory phenotype with adaptive immune resistance.However,the EGFR-mutant or ALK-rearranged groups showed a remarkably higher proportion of PD-L1-/TIL-tumors,suggesting an uninflamed phenotype with immunological ignorance.Notably,similar to triple wild-type NSCLC tumors,EGFR L858R-mutant tumors positively correlated with an inflammatory phenotype,suggesting responsiveness to anti-PD-1/PD-L1 immunotherapy(P<0.05).Furthermore,the CIBERSORT algorithm results revealed that EGFR-mutant and ALK-rearranged tumors were characterized by an enriched resting memory CD4+T cell population(P<0.001),as well as a lack of CD8+T cells(P<0.01),and activated memory CD4+T cells(P=0.001).Conclusions:Our study highlighted the complex relationships between immune heterogeneity and immunotherapeutic responses in East Asian NSCLC patients regarding oncogenic dependence.

The Antarctic Oscillation-East Asian Summer Monsoon Connections in NCEP-1 and ERA-40

Connections between the spring Antarctic Oscillation （AAO） and the East Asian summer monsoon （EASM） in two reanalysis datasets-NCEP-1 （NCEP/NCAR Reanalysis 1） and ERA-40 （ECMWF 40- year Reanalysis）-are investigated in this study. Both show significant correlation between AAO and EASM rainfall over the Yangtze River valley, especially after about 1985. Though ERA-40 shows weaker anomalous signals connecting AAO and EASM over southern high latitudes than NCEP-1, both datasets reveal similar connecting patterns between them. A wave-train-like pattern appears in the upper levels, from southern high latitudes through east of Australia and from the Maritime Continent to East Asia. In positive AAO years, the cross equatorial southeasterly flow over the Maritime Continent in the lower levels is strengthened, the specific humidity of the whole atmosphere over East Asia increases, and convective activity is enhanced; thus the summer rainfall over East Asia increases. The spring AAO-EASM connection may be better represented in ERA-40.

An Introduction to the Integrated Climate Model of the Center for Monsoon System Research and Its Simulated Influence of El Ni?no on East Asian–Western North Pacific Climate

This study introduces a new global climate model--the Integrated Climate Model （ICM）--developed for the seasonal prediction of East Asian-western North Pacific （EA-WNP） climate by the Center for Monsoon System Research at the Institute of Atmospheric Physics （CMSR, IAP）, Chinese Academy of Sciences. ICM integrates ECHAM5 and NEMO2.3 as its atmospheric and oceanic components, respectively, using OASIS3 as the coupler. The simulation skill of ICM is evaluated here, including the simulated climatology, interannual variation, and the influence of E1 Nifio as one of the most important factors on EA-WNP climate. ICM successfully reproduces the distribution of sea surface temperature （SST） and precipitation without climate shift, the seasonal cycle of equatorial Pacific SST, and the precipitation and circulation of East Asian summer monsoon. The most prominent biases of ICM are the excessive cold tongue and unrealistic westward phase propagation of equatorial Pacific SST. The main interannual variation of the tropical Pacific SST and EA-WNP climate E1 Nifio and the East Asia-Pacific Pattern--are also well simulated in ICM, with realistic spatial pattern and period. The simulated E1 Nifio has significant impact on EA-WNP climate, as in other models. The assessment shows ICM should be a reliable model for the seasonal prediction of EA-WNP climate.

吗啡诱导大鼠镇痛耐受和脊髓GIRK1-2表达减少

【目的】观察G蛋白门控内向整流钾离子通道(GIRK)亚单位GIRK1和GIRK2在吗啡耐受大鼠脊髓背角的表达变化并探讨其调控机制。【方法】成年雄性SD大鼠连续7 d鞘内注射吗啡(15μg/d)建立吗啡耐受模型。在每天吗啡注射前30 min,鞘内注射蛋白激酶C-ε(PKCε)选择性抑制剂εV1-2(10μg),观察对吗啡耐受以及脊髓背角GIRK1和GIRK2表达的影响。24只大鼠随机平均分成四组:生理盐水组(saline)、吗啡组(morphine)、吗啡+生理盐水组(morphine+saline)和吗啡+εV1-2组(morphine+εV1-2)。所有大鼠在1 d、3 d、5 d和7 d,药物注射前和吗啡注射后30 min后检测热痛阈值,在第7天行为学测试结束后,免疫荧光检测脊髓背角GIRK1和GIRK2的表达。【结果】荧光双染显示,GIRK1和GIRK2主要分布于大鼠脊髓背角I-Ⅱ板层,且与μ阿片受体(MOR)共染。与生理盐水组相比,连续7 d鞘内注射吗啡导致吗啡镇痛效应显著下降(P<0.001),同时导致脊髓背角GIRK1(22.45±10.58vs.62.83±20.80,P<0.001)和GIRK2(23.67±8.78 vs.50.17±11.05,P=0.001)表达显著降低。荧光双染显示,PKCε与GIRK1和GIRK2在脊髓背角共染。鞘内注射εV1-2可以有效抑制吗啡耐受的形成(P<0.001),且抑制吗啡诱导的GIRK1(54.50±10.37 vs.19.33±9.48,P<0.001)和GIRK2(39.83±6.24 vs.15.83±9.58,P=0.001)表达降低。【结论】脊髓背角GIRK1和GIRK2下调与吗啡耐受密切相关,PKCε是吗啡诱导GIRK1和GIRK2下调的重要原因。

LncRNA KCNQ1OT1靶向miR-9-5p对口腔癌细胞黏附性及活性的影响

目的探究长链非编码RNA钾电压门控通道亚家族Q成员1反向转录物1(LncRNA KCNQ1OT1)靶向miR-9-5p对口腔鳞状细胞癌细胞黏附性及活性的影响。方法体外培养口腔癌SCC25细胞,分别转染LncRNA KCNQ1OT1阴性对照、LncRNA KCNQ1OT1 siRNA、miR-9-5p阴性对照、miR-9-5p siRNA、LncRNA KCNQ1OT1 siRNA和miR-9-5p siRNA,分别记为KCNQ1OT1-NC组、KCNQ1OT1组、miR-9-5p-NC组、miR-9-5p组,KCNQ1OT1+miR-9-5p组及口腔癌组;采用RT-PCR检测各组细胞的LncRNA KCNQ1OT1及miR-9-5p水平,MTT法检测细胞吸光度(OD)值,流式细胞仪检测细胞凋亡率,Western blot检测细胞中CD44S及CD44V5蛋白表达;通过双荧光素酶报告证实LncRNA KCNQ1OT1与miR-9-5p靶向关系。结果KCNQ1OT1组LncRNA KCNQ1OT1水平低于口腔癌组(P<0.05),miR-9-5p组miR-9-5p水平低于口腔癌组(P<0.05);与口腔癌组相比,KCNQ1OT1组、miR-9-5p组、KCNQ1OT1+miR-9-5p组细胞OD值、CD44S及CD44V5蛋白降低,细胞凋亡率升高(P<0.05),且以KCNQ1OT1+miR-9-5p组效果最为显著(P<0.05);双荧光素酶报告结果显示,miR-9-5p是LncRNA KCNQ1OT1的靶基因。结论LncRNA KCNQ1OT1可通过调控miR-9-5p表达从而降低口腔鳞状细胞癌细胞黏附性,抑制口腔鳞状细胞癌细胞增殖,诱导其凋亡。

温针灸对兔膝骨关节炎软骨中ASC、Caspase-1和P2X7蛋白表达的影响

目的 观察温针灸对膝骨关节炎(KOA)模型兔关节软骨组织中凋亡相关斑点样蛋白(ASC)、半胱氨酸蛋白酶-1(Caspase-1)、嘌呤能离子通道型受体7(P2X7)表达的影响,研究温针灸治疗KOA的作用机制。方法 取40只雄性新西兰兔随机分为空白组、模型组、抑制剂组和温针灸组,每组10只。除空白组外,其余各组采用经典右后肢膝关节伸直位,用石膏管型固定4周制备兔KOA模型。造模成功后,各组给予相应干预措施。应用Lequesne MG评分量表评估兔膝关节状态改变与行为学改变,HE染色观察膝关节软骨病理形态学改变,免疫组织化学法和Western blot法检测软骨组织中ASC、Caspase-1、P2X7蛋白的表达,免疫荧光检测Caspase-1蛋白的表达。结果 造模前,各组实验兔Lequesne MG评分差异无统计学意义(P>0.05);造模后,与空白组相比,其余组Lequesne MG评分均上升(P<0.05);干预治疗后,与模型组比较,温针灸组和抑制剂组评分降低(P<0.05)。HE染色显示,空白组软骨表面结构完整,软骨细胞排列均匀;模型组软骨表面粗糙不平,软骨受损明显,软骨细胞形态大小不一,排列紊乱;抑制剂组和温针灸组软骨表面相对光滑、完整,软骨细胞分布较为均匀,软骨层结构相对清晰。与空白组比较,模型组Mankin’s评分升高(P<0.05);与模型组比较,温针灸组和抑制剂组Mankin’s评分降低(P<0.05)。免疫组织化学法、免疫荧光及Western blot检测结果显示,与空白组比较,模型组ASC、Caspase-1、P2X7的表达均升高(P<0.05);与模型组比较,温针灸组和抑制剂组ASC、Caspase-1、P2X7的表达均降低(P<0.05);温针灸组和抑制剂组相比,ASC、Caspase-1、P2X7表达差异均无统计学意义(P均>0.05)。结论 温针灸可减轻兔KOA软骨损伤,其机制可能与ASC、Caspase-1、P2X7表达降低及细胞焦亡抑制有关。

Environmental anomalies in the northeastern East China Sea during the last 3 000 years:implications for El Nio activity in the Holocene

To reconstruct the productivity changes for the last 10 500 a in the northeastern East China Sea （ECS）, biogenic compounds （such as carbonate, organic carbon and opal）, marine micropaleontological fossils （planktonic foraminifera, benthic foraminifera, radiolarian and silicoflagellate） and the compositional characters of benthic foraminifera fauna analyses were carried out on a sediment core DOC082 obtained from the western slope of Okinawa Trough （29°13.93′N, 128°08.53′E; 1 128 m water depth）. The long-term changes of biogenic and micropaleontological proxies display some similarities through the last 10 500 a, which show three different phases： lower values are recorded during the early and middle ttolocene （before about 4 000 a BP）, followed by an abrupt and remarkable increase at about 4 000 a BP, the late Holocene （after about 3 000 a BP） is characterized by continuously high values. The multi-proxy data of paleoproductivity and percents of benthic foraminifera genera （Uvigerina and Bulimina） show that during the early and middle Holocene （10 500-4 000 a BP） productivity was relatively low with a sudden and distinct increase at about 4 000 a BP, and the late Holocene （3 400-0 a BP） is marked by significantly higher productivity. Also, the radiolarian-based sea surface temperature （SST） records reveal a distinct decline in SST in the late Holocene after 3 200 a BP, very different from the early and middle Holocene. For the last 3 000 a, the enhanced biological productivity and distinctly lower SST indicate a major change of oceanographic conditions in the northeastern ECS. These marine environmental anomalies are consistent with other paleoclimatic records for the late Holocene in the Chinese continent and its surrounding regions. After analyzing the mechanisms of modern productivity and SST changes in the northeastern ECS, and based on the climatic anomalies in the Chinese continent and variations in the Kuroshio Current during modern El Nino periods, we suggest that the anomalous environmental conditions in the northeastern ECS may imply intensified El Nino activity during the late Holocene.

基于1DCNN-GRU的启闭机液压系统故障诊断

由于启闭机液压系统内部结构复杂,故障信号不易采集,使用AMESim软件搭建启闭机液压系统仿真模型,构建6种典型故障数据集。基于这些数据集,提出一维卷积神经网络(1 Dimensional Convolutional Neural Network,1DCNN)与门控循环单元(Gated Recurrent Unit,GRU)相结合的故障诊断方法,利用1DCNN提取信号数据的空间特征和GRU提取信号数据的时间特征,实现对信号数据空间及时间特征的融合,并对融合特征进行分类识别。

改进灰色GM(1,1)模型的EAST快控电源输出电流预测

针对非模型PID控制难以克服参数变化、时滞的固有缺陷,为优化托卡马克装置中应对等离子体垂直不稳定位移的主动反馈控制,通过改进灰色GM(1,1)预测模型对基于级联H桥拓扑的EAST快控电源的输出电流进行准确预测以优化控制参数。灰色GM(1,1)预测模型适用于小样本、贫信息系统,所需建模样本少、计算简易。预测拟合序列的差异导致在对输出电流的上凸序列进行灰色GM(1,1)建模时存在较大预测误差,选用一种将上凸序列轴对称变换为上凹序列并建立非等间距灰色GM(1,1)预测模型的数据变换方法,同时利用样本点给出了非等间距序列的预测时刻的估计式。基于该改进灰色GM(1,1)预测模型,推导了预测模型的建模过程,通过仿真比较两种灰色GM(1,1)预测模型对电源输出电流的预测误差,改进后突变段预测误差率降低至10%以下,并在实例分析中验证改进灰色GM(1,1)预测模型的有效性。

Minimum Bedrock Exposure Ages and Their Implications:Larsemann Hills and Neighboring Bolingen Islands,East Antarctica

Considerable controversy exists over whether or not extensive glaciation occurred during the global Last Glacial Maximum（LGM） in the Larsemann Hills.In this study we use the in situ produced cosmogenic nuclide ^（10）Be（half life 1.51 Ma） to provide minimum exposure ages for six bedrock samples and one erratic boulder in order to determine the last period of deglaciation in the Larsemann Hills and on the neighboring Bolingen Islands.Three bedrock samples taken from Friendship Mountain（the highest peak on the Mirror Peninsula,Larsemann Hills;～2 km from the ice sheet） have minimum exposure ages ranging from 40.0 to 44.7 ka.The erratic boulder from Peak 106（just at the edge of the ice sheet） has a younger minimum exposure age of only 8.8 ka.The minimum exposure ages for two bedrock samples from Blundell Peak（the highest peak on Stornes Peninsula,Larsemann Hills;～2 km from the ice sheet） are about 17 and 18 ka.On the Bolingen Islands（southwest to the Larsemann Hills;～10 km from the ice sheet）,the minimum exposure age for one bedrock sample is similar to that at Friendship Mountain（i.e.,44 ka）.Our results indicate that the bedrock exposure in the Larsemann Hills and on the neighboring Bolingen Islands commenced obviously before the global LGM（i.e.,20-22 ka）,and the bedrock erosion rates at the Antarctic coast areas may be obviously higher than in the interior land.

Geochemical Constrains on MORB Composition and Magma Sources at East Pacific Rise Between 1°S and 2°S

The East Pacific Rise(EPR)is a typical fast spreading ridge.To gain a better understanding of the magmatism under ridges,Mid Ocean Ridge Basalts(MORBs)with remarkably heterogeneous compositions are obtained from(EPR)1?–2?S and multielement geochemical and radioisotope analyses are conducted.Results show that these MORBs have wide variation ranges in trace element concentrations and isotopic ratios.Sample 07 has low concentrations of incompatible elements,and very low ^(87)Sr/^(86)Sr,and high ^(143)Nd/^(144)Nd from 0.70213 to 0.702289 and 0.513234 to 0.513289,respectively.However,other samples show enrichment in incompatible elements to varying degrees,and medium values of ^(87)Sr/^(86)Sr and ^(143)Nd/^(144)Nd from 0.702440 to 0.702680 and 0.513086to 0.513200,respectively.This study proposes that one depleted source and two enriched sources contribute to the formation of MORBs from EPR 1?–2?S.Samples 02 and 10 are formed by mixing between one enriched source and one depleted source,while sample 07 is crystallized from the depleted source with no mixing process involved.However,the formation of samples 06 and 11are different,and thus further research is required to determine genesis.

基于Sentinel-1遥感数据的东洞庭湖水文特征动态监测

水文特征的动态变化对于农业生产、防洪泄洪、水文循环以及湿地生态系统的稳定性及其生物多样性有直接影响,通过高时空分辨率的遥感影像对湖泊水文特征进行动态监测显得尤为重要。本研究基于Google Earth Engine(GEE)云平台、Sentinel-1(VV)雷达影像数据,使用Otsu法对东洞庭湖水体进行提取,应用台体公式结合城陵矶水文站的水位数据计算湖泊月度水量变化,再基于TRMM-3B43降水数据与水文站月平均径流量分析湖泊水量与洞庭湖流域降雨以及径流量的变化关系。结果表明:(1)东洞庭湖多年平均水体面积为565.39 km^(2),峰值为1228.84 km^(2)(2020年7月),谷值为188.63 km^(2)(2019年12月)。(2)东洞庭湖月度面积与城陵矶水文站的月度水位具有明显的线性关系,两者回归方程的R 2达到0.975。(3)随着浸没率上升,西侧湖泊范围扩大的连续性要强于东侧,说明东洞庭湖西侧湖底地形起伏较小。(4)历年湖泊水量达峰时间相较于流域降雨滞后一个月且两者波形高度一致。(5)东洞庭湖的湖水持续从位于湖泊东北角城陵矶的通江口流入长江,其径流量随季节波动明显并与相对水量变化具有较强一致性。本研究可为洞庭湖地区的灌溉管理、汛期洪水调蓄等实际应用提供参考,也为Sentinel-1数据在湖泊水文分析上的应用提供一种可行方案。

Molecular characterization and phylogenetic analysis of Middle East 2009 H1N1 pdm isolates

Objective:To study hemagglutinin genetic evolution of some Middle East(ME) 2009 H1N1 pdm isolates and compared them with prototype vaccine strain[A/California/07/2009(H1N1)],which is used as a vaccine strain in the Northern Hemisphere 2010-2011.Methods:Nucleotide and/ or amino acid sequences of HA gene of fifty-four ME 2009 H1N1 pdm isolates were retrieved from GenBank Database by using Basic BLAST engine.Phylogenetic trees were established for both nucleotide and amino acid sequences using the muscle algorithm of the computer program CLC free workbench 5.6.1 JRE software.Amino acids alignment was also done to compare sequences HA1 domains of HA genes of ME 2009 H1N1 pdm isolates(n=39) with amino acid sequence of prototype vaccine strain A/California/07/2009(H1N1).Results:Phylogenetic analysis of amino acids and nucleotides of the HA gene of the ME 2009 H1N1 pdm isolates confirmed their evolutionary position in cluster with prototype vaccine strain(A/California/07/2009(H1N1)) which is used as vaccine strain in the Northern Hemisphere 2010-2011.Antigenically,the ME 2009 H1N1 pdm isolates were homogeneous and closely related to prototype vaccine.Only a few amino acid substitutions in the HA among the ME 2009 H1N1 pdm isolates were analyzed.Conclusions: The current influenza vaccine is expected to provide a good protection against ME 2009 H1N1 pdm because it contains strains with H1HA[A/California/07/2009(H1N1)]-like strain.

电压门控钾通道亚家族G成员1在肺癌中的表达及生物学作用

目的:探讨电压门控钾通道亚家族G成员1(potassium voltage-gated channel subfamily G member 1,KCNG1)在人肺癌组织中的表达水平和临床意义以及其在肺癌细胞恶性生物学行为中的作用。方法:通过TCGA数据库(The Cancer Genome Atlas)分析KCNG1 mRNA在人肺癌组织中的表达水平,探究其与肺癌患者临床病理特征及预后的关系;基于KCNG1 mRNA表达水平构建预测肺癌患者预后的列线图模型;采用基因本体(GO)功能富集分析和京都基因与基因组百科全书通路(KEGG)富集分析探究KCNG1潜在的生物学功能;采用基因集富集分析(GSEA)预测KCNG1相关差异表达基因参与调控的相关信号通路。采用实时荧光定量PCR(qRT-PCR)及蛋白免疫印迹分别检测肺癌A549和H1299细胞系以及正常肺上皮细胞中KCNG1 mRNA和蛋白表达水平;通过转染siRNA构建KCNG1敲减的细胞株,分别采用EdU,Transwell,Matrigel Transwell,细胞划痕愈合及血管生成拟态实验检测细胞株生物学行为变化。结果:KCNG1 mRNA在肺癌组织中显著高表达且与肺癌患者不良预后密切相关(P均<0.05);列线图模型初步证实KCNG1可能是肺癌潜在的生物标志物,并具有良好的预后评价功能;GO及KEGG富集分析提示KCNG1在调节激素分泌、离子转运、神经肽信号通路及细胞间黏附等生物学过程中发挥重要作用;GSEA结果提示KCNG1相关差异表达基因主要富集在KRAS,MTORC1,MYC,P53及WNT信号通路;KCNG1敲低的肺癌细胞增殖、迁移、侵袭和成管能力明显受到抑制(P均<0.05)。结论:KCNG1 mRNA在肺癌中显著高表达且与患者不良预后密切相关;siRNA介导的KCNG1敲低可显著抑制肺癌细胞的恶性生长。

Oscillation of S5 helix under different temperatures in determination of the open probability of TRPV1 channel

Transient receptor potential vanilloid subtype 1 (TRPV1) is a polymodel sensory receptor and can be activated by moderate temperature (≥ 43 ℃). Though extensive researches on the heat-activation mechanism revealed some key elements that participate in the heat-sensation pathway, the detailed thermal-gating mechanism of TRPV1 is still unclear. We investigate the heat-activation process of TRPV1 channel using the molecular dynamics simulation method at different temperatures. It is found that the favored state of the supposed upper gate of TRPV1 cannot form constriction to ion permeation. Oscillation of S5 helix originated from thermal fluctuation and forming/breaking of two key hydrogen bonds can transmit to S6 helix through the hydrophobic contact between S5 and S6 helix. We propose that this is the pathway from heat sensor of TRPV1 to the opening of the lower gate. The heat-activation mechanism of TRPV1 presented in this work can help further functional study of TRPV1 channel.

A novel enhancement mode AlGaN/GaN high electron mobility transistor with split floating gates

A novel enhancement-mode AlGaN/GaN high electron mobility transistor（HEMT） is proposed and studied.Specifically,several split floating gates（FGs） with negative charges are inserted to the conventional MIS structure.The simulation results revealed that the V_（th） decreases with the increase of polarization sheet charge density and the tunnel dielectric（between FGs and AlGaN） thickness,while it increases with the increase of FGs sheet charge density and blocking dielectric（between FGs and control gate） thickness.In the case of the same gate length,the V_（th） will left shift with decreasing FG length.More interestingly,the split FGs could significantly reduce the device failure probability in comparison with the single large area FG structure.

A subsurface intensity index of the cold eddy in the East China Sea

The Cold Eddy in the East China Sea(CEECS) is located about 150 km southwest of Cheju Island.This region experiences a complex current system under the influences of the Yellow Sea Warm Current(YSWC),the Yellow Sea Coastal Current(YSCC),and the northward Kuroshio residual.To identify the strength of the CEECS,a simple subsurface intensity index is developed.Because the CEECS can be traced by temperature minimum,the intensity index is determined by the difference in sea temperature averaged across cores within and surrounding the region.Based on SODA,the CEECS subsurface intensity index time series can be calculated,with which the inter-annual variation of the CEECS is analyzed.

小电导的钙激活钾离子通道1的真核表达及其在乳腺癌细胞增殖中的作用

目的构建重组的真核表达质粒pENTER-小电导的钙激活钾离子通道1(small conductance calcium-gated K+channel 1,SK_(Ca)1),并研究其在乳腺癌细胞密歇根癌症基金会7号(Michigan cancer foundation-7,MCF-7)中的表达;观察SK_(Ca)1的亚细胞定位;检测SK_(Ca)1在乳腺癌细胞增殖中的作用。方法从MCF-7细胞中抽提总RNA并逆转录成cDNA;以cDNA为模板扩增SK_(Ca)1基因,通过无缝克隆技术将基因片段克隆至真核表达质粒pENTER中;质粒转染MCF-7细胞后,分别用Western blot和免疫荧光实验检测SK_(Ca)1的表达及亚细胞定位,用细胞计数试剂盒8(cell counting kit-8,CCK-8)实验测定SK_(Ca)1的细胞增殖效应。结果成功构建了带有标签的重组真核表达质粒pENTER-SK_(Ca)1,并在乳腺癌细胞MCF-7中高效表达;SK_(Ca)1主要分布于细胞质和细胞核,并能促进乳腺癌细胞增殖。结论成功制备了研究SK_(Ca)1的必要工具原料并对其分子机制进行了初步探索,为深入研究SK_(Ca)1在乳腺癌细胞中的信号转导作用奠定了基础。

lncRNA KCNQ1OT1调控miR-384/CACNA1C轴对心肌细胞增殖、凋亡的影响

目的探讨长链非编码RNA钾电压门控通道亚家族Q成员1反向转录物1(lncRNA KCNQ1OT1)调控miR-384/L型钙离子通道α1C亚基基因(CACNA1C)轴对心肌细胞增殖、凋亡的影响。方法实时荧光定量PCR(qRT-PCR)、Western blot分别检测正常培养的大鼠心肌H9c2、CP-R073细胞及缺氧/复氧(H/R)诱导的H9c2、CP-R073细胞中的KCNQ1OT1、miR-384、CACNA1C蛋白表达。将H9c2细胞分为Ct组、Model组、si-NC组、si-KCNQ1OT1组、mimic NC组、miR-384 mimic组、si-KCNQ1OT1+inhibitor NC组、si-KCNQ1OT1+miR-384 inhibitor组。除Ct组外,其他组H9c2细胞均需转染对应物质后构建H/R损伤模型。qRT-PCR检测细胞中KCNQ1OT1、miR-384表达;CCK-8法、EdU染色检测细胞增殖;流式细胞术检测细胞凋亡;ELISA法检测细胞中肌红蛋白(Mb)、肌钙蛋白-Ⅰ(cTnⅠ)水平;Western blot检测CACNA1C、增殖细胞核抗原(PCNA)、半胱氨酰天冬氨酸特异性蛋白酶-3(Caspase-3)、Bcl-2相关X蛋白(Bax)蛋白表达;双荧光素酶报告基因实验验证KCNQ1OT1与miR-384、miR-384与CACNA1C的关系。结果H/R诱导的H9c2、CP-R073细胞中KCNQ1OT1、CACNA1C蛋白表达升高,miR-384表达降低,且H/R诱导的H9c2细胞中KCNQ1OT1、CACNA1C蛋白表达最高,miR-384表达最低,因此,后续选择H9c2细胞为研究对象。与Ct组比较,Model组细胞中KCNQ1OT1、细胞凋亡率、Mb、cTnⅠ水平、CACNA1C、Caspase-3、Bax蛋白表达升高,miR-384表达、D 450值、EdU阳性率、PCNA蛋白表达降低(P<0.05);沉默KCNQ1OT1或过表达miR-384可促进H/R诱导的H9c2细胞增殖,抑制细胞凋亡;miR-384 inhibitor减弱了沉默KCNQ1OT1对H/R诱导的H9c2细胞增殖的促进作用,以及对细胞凋亡的抑制作用;KCNQ1OT1靶向调控miR-384/CACNA1C轴。结论沉默KCNQ1OT1可能通过上调miR-384来抑制CACNA1C表达,进而促进H/R诱导的H9c2细胞增殖,抑制细胞凋亡。